Preclinical safety evaluation of the ethanolic extract from campomanesia guazumifolia (cambess.) O. Berg fruits peels in rats.

The toxicological potential of the ethanolic extract from Campomanesia guazumifolia (EECG), a species traditionally recognised for its antidiabetic, anti-inflammatory and hypercholesterolemic properties, was investigated in acute and subacute toxicity models in rats. In the acute toxicity test, 2000 mg/kg of EECG was administered orally in female rats, while male and female rats received 250, 500 or 750 mg/kg of EECG for the subacute toxicity test. No evidence of toxicity was observed in the animals acutely exposed, indicating that the LD50 is above 2000 mg/kg. However, repeated exposure to this extract resulted in alterations in important biochemical parameters indicative of hepatic and renal toxicity, including AST, ALT, creatinine, urea, and cholesterol. Additionally, some hematological parameters were also changed by the treatment. EECG demonstrated low toxicological potential. Nevertheless, given the observed changes in liver and kidney enzymes, further investigations into the protective effects of this extract following repeated administration are warranted.

Can exposure to lisdexamfetamine dimesylate from juvenile period to peripubertal compromise male reproductive parameters in adult rats?

Lisdexamfetamine (LDX) is a d-amphetamine prodrug used to treat attention deficit and hyperactivity disorder, a common neurodevelopmental disorder in children and adolescents. Due to its action mediated by elevated levels of catecholamines, mainly dopamine and noradrenaline, which influence hormonal regulation and directly affect the gonads, this drug may potentially disrupt reproductive performance. This study evaluated the effects of exposure to LDX from the juvenile to peripubertal period (critical stages of development) on systemic and reproductive toxicity parameters in male rats. Male Wistar rats (23 days old) were treated with 0; 5.2; 8.6 or 12.1 mg/kg/day of LDX from post-natal day (PND) 23 to 53, by gavage. LDX treatment led to reduced daily food and water consumption, as well as a decrease in social behaviors. The day of preputial separation remained unaltered, although the treated animals exhibited reduced weight. At PND 54, the treated animals presented signs of systemic toxicity, evidenced by a reduction in body weight gain, increase in the relative weight of the liver, spleen, and seminal gland, reduction in erythrocyte and leukocyte counts, reduced total protein levels, and disruptions in oxidative parameters. In adulthood, there was an increase in immobile sperm, reduced sperm count, morphometric changes in the testis, and altered oxidative parameters, without compromising male sexual behavior and fertility. These findings showed that LDX-treatment during the juvenile and peripubertal periods induced immediate systemic toxicity and adversely influenced reproductive function in adult life, indicating that caution is necessary when prescribing this drug during the peripubertal phase.

A mixture of glyphosate and 2,4-D herbicides enhances the deleterious reproductive outcomes induced by Western diet in obese male mice.

The consumption of Western diet (WD) - enriched in fats and sugars - is associated with overweight, obesity and male reproductive disorders. In addition to WD intake, crops and dairy products display residues of herbicides, including glyphosate and 2,4-D that are widely applied worldwide. The concomitant exposure to WD and herbicides - mimicking contemporary scenarios - is not fully investigated. Thus, we evaluated the effects of glyphosate and 2,4-D, alone or in mixture, on WD-induced alterations in the male genital system. Male C57BL6J mice were submitted to WD (chow containing 20% lard, 0.2% cholesterol, 20% sucrose, and high sugar solution with 23.1 and 18.9 g/L of D-fructose and D-glucose) for 6 months. Concomitantly to WD, the animals received glyphosate (0.05, 5, or 50 mg/kg/day), 2,4-D (0.02, 2 or 20 mg/kg/day) or their mixture (0, 05 + 0.02, 5 + 2, or 50 + 20 mg/kg/day) by intragastrical administration (5×/week). Doses were based on Acceptable Daily Intake (ADIs) or No Observed Adverse Effect Level (NOAEL) values. Herbicide exposure did not alter the WD-induced obesity, hypercholesterolemia and hyperglycemia. WD induced sperm cell abnormalities, reduced the number, volume and area of Leydig cells, enhanced the frequency of epididymal abnormalities, decreased the proliferation in both germinal and epididymal epithelia, and reduced the number of androgen receptor (AR) positive epididymal cells. Remarkably, the herbicide mixtures promoted such WD-induced effects: increased the frequency of sperm cell and epididymal abnormalities (absence of sperm, cytoplasmic vacuoles, and clear cell hypertrophy) (5 + 2 and 50 + 20 doses); decreased Leydig cell nuclei volume and area (5 + 2 and 50 + 20 doses), reduced epididymal cell proliferation (all mixtures), and AR expression (50 + 20 dose). In addition, herbicide mixtures reduced serum testosterone levels (5 + 2 and 50 + 20 doses). Our findings indicate that the mixture of glyphosate and 2,4-D herbicides, mimicking environmentally relevant scenarios, promotes WD-induced changes in the male genital system.

Maternal-fetal safety evaluation of an aqueous extract of Casearia sylvestris leaves in rats.

BACKGROUND: This study evaluated the maternal, embryotoxic, and teratogenic effects of the aqueous extract of Casearia sylvestris (AECS), a species listed in the Unique Health System of Brazil, and widely used for treating several conditions, such as diarrhea, wounds, pain, and ulcers. METHODS: Pregnant rats were daily treated orally with 0, 175, 350, or 700 mg/kg/body weight of AECS, from gestational day (GD) 6 to 15 (organogenesis period). On GD 20, the pregnant rats were euthanized, and the litters submitted to an assessment of fetal development. RESULTS: No clinical signs of toxicity were observed in the dams during the treatment. In the embryo-fetal development study, a significant increase in the basal zone height of the placenta was observed in the intermediate dose group. Furthermore, there was a significant increase in the relative anogenital distance measurement of female fetuses in the lowest and intermediate dose groups. Although no visceral abnormalities were observed in the treated-fetuses, skeletal anomalies evidenced by changes in the ossification of the sternum and the presence of supernumerary ribs were found in the intermediate and high dose groups. CONCLUSION: In conclusion, the treatment with AECS during organogenesis at this dose level had detrimental effects on the normal development of fetuses.

Insights from the maternal lineage of the F2 generation after exposure to an environmentally relevant dose of benzo(a)pyrene in the male rats of F0 generation.

Benzo(a)pyrene (BaP) is a substance with the potential to induce endocrine disruption in the F0 generation and cause adverse multigenerational effects (F1 generation) for reproductive parameters in rats. The objective of this study was to investigate the occurrence of transgenerational inheritance in the reproductive aspects of male and female rats belonging to the F2 generation (MF2). This investigation was conducted following the exposure of male rats from the F0 generation to BaP to assess potential effects on subsequent generation from the maternal lineage (F1). For that, juvenile male Wistar rats (F0) were orally exposed to BaP (0.1 µg/kg/day) for 31 consecutive days. In adulthood, they were mated with untreated females to obtain female offspring (F1), which later produced the MF2. In the MF2 generation, both males and females exhibited increased body weight on postnatal day (PND) 1. In MF2 males, we observed delayed preputial separation, altered pup weight, reduced levels of follicle-stimulating hormone (FSH), increased intratesticular testosterone levels, decreased type A sperm, epididymal disturbances, reduced 5 α-reductase activity, increased testicular proliferation, and alterations in testicular antioxidant enzymes. In MF2 females, we noted morphological uterine enlargement, reduced sexual activity, and decreased progesterone levels. The findings suggest that the alterations observed in both MF2 males and females can be attributed to modifications in the sperm from F0 generation, which were subsequently transmitted to F1 females and MF2 generation due to BaP exposure.

Safety of lactational exposure to venlafaxine on the rat mammary gland development and carcinogenesis in F1 female offspring.

The chronic use of selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors (SNRIs) may result in human gynecomastia, mammoplasia, galactorrhea, and elevated breast cancer risk. As antidepressants are frequently used for postpartum depression (PPD) treatment, this study investigated the adverse effects of lactational exposure to venlafaxine (VENL, a selective SNRI) on mammary gland development and carcinogenesis in F1 female offspring. Thus, lactating Wistar rats (F0) received VENL by oral gavage at daily doses of 3.85, 7.7, or 15.4 mg/kg (N = 9, each group) from lactational day (LD 1) until the weaning of the offspring (LD 21). F1 female offspring were euthanized for mammary gland, and ovary histological analyses on the post-natal day (PND) 22 and 30 (1 pup/litter/period, N = 9, each group). At PND 22, other females (2 pups/litter, N = 18, each group) received a single dose of carcinogen N-methyl-N-nitrosourea (MNU, 50 mg/kg) intraperitoneally (i.p.) for tumor susceptibility assay until PND 250. Tumor incidence and latency were recorded and representative tumor samples were collected for histopathology. The results indicate that lactational exposure to VENL did not alter the development of the mammary gland (epithelial ductal tree or the mean number of terminal end buds), or the ovary (weight and primary, secondary, tertiary, and Graafian follicles) in prepubertal F1 female offspring. In addition, VENL exposure did not influence tumor incidence or tumor latency in adult female offspring that received MNU. Thus, the findings of this animal study indicated that lactational VENL exposure, a period similar to human PPD, did not exert an adverse effect on the mammary gland development at the prepubertal phase or on chemically induced mammary tumorigenesis in adult F1 female rats.

Paternal low-dose benzo(a)pyrene exposure in rats impairs sexual development and fertility of the paternal lineage in F2 generation: A transgenerational study.

The field of Paternal Origins of Health and Disease (POHaD) is highly relevant but remains under-explored. The F2 generation from males indirectly exposed (F1 - via germ cells) to benzo(a)pyrene (BaP), named PF2, was investigated in this study under parameters of sexual development and reproductive performance of male and female rats. Male Wistar rats (F0) were exposed to BaP (0.1 µg/kg/day) for 31 consecutive days (gavage) during prepuberty. The F0 rats were mated with untreated females to produce male offspring (F1), which were exposed to BaP via germ cells. The F1 males were later mated with untreated females to obtain the PF2 generation, which was the focus of our investigation. Our findings showed that PF2 males exhibited a decrease in anogenital distance, fertility potential, testosterone levels, and type A sperm. Meanwhile, PF2 females had an earlier vaginal opening, lower lordosis scores, and decreased fertility. Furthermore, changes in the histomorphology of the testis/epididymis and ovary/uterus were observed. The repercussions of the PF2 generation indicate that these animals showed losses in both sexual development and fertility potential, and we can conclude that this damage remained due to paternal transgenerational inheritance caused by a low dose of BaP.

Gestational exposure to continuous light impairs the development of the female reproductive system in adult Wistar rat offspring.

INTRODUCTION: It has been suggested that maternal exposure to constant light during the gestational period could be considered as a chronic stressor, impairing offspring development by interfering in neuroendocrine and behavior responses. OBJECTIVE: This study aimed to evaluate whether maternal exposure to continuous light during pregnancy affects the adult reproductive system in the female offspring. MATERIALS AND METHODS: Pregnant Wistar rats were allocated into light-dark (LD) group, exposed to light and dark photoperiod during gestation, and the light-light (LL) group, exposed to a photoperiod of constant light during gestation. After birth, pups were maintained under normal light-dark photoperiod until adulthood. At postnatal day 90, blood was collected from the female offspring, to analyze plasma luteinizing hormone (LH) and progesterone levels, and the uterus and ovaries were harvested for morphometric, histological, and oxidative stress evaluations. RESULTS AND DISCUSSION: Female exposure to continuous light during the intrauterine period resulted in the adult reduction of LH and increased progesterone plasma levels, and uterine injuries a higher number of endometrial glands and reduced levels of antioxidant enzymes, such as glutathione reductase and glutathione S-transferase. In these experimental conditions, gestational continuous light exposure disturbs sex hormone balance and reduces the antioxidant enzymatic activity in the uterus of female offspring in adult life.

Embryo-fetal safety evaluation of ondansetron in rats.

BACKGROUND: Ondansetron is a 5HT3 receptor antagonist, used to mitigate the effects of nausea and vomiting after chemotherapy or surgery. Since nausea and vomiting are common experiences during the first trimester of pregnancy, this antiemetic has been the main drug used during this period. METHODS: To evaluate the effects of ondansetron on the embryo-fetal development, which are still very contradictory, pregnant rats were exposed to therapeutic doses of ondansetron (1.7 or 2.5 mg/kg) daily, from gestational day (GD) 6 to 15. RESULTS: No clinical signs of toxicity were observed in dams during the treatment. Although the hemato-biochemical parameters were similar among the groups, histological changes, as well as a reduction in the weight of kidney were found in the treated dams. After fetal examination, no visceral and skeletal abnormalities were observed in treated fetuses. CONCLUSION: In conclusion, therapeutic doses of ondansetron have low teratogenic potential in rats. These data provide important information about the drug safety during pregnancy.

Analgesic and anti-inflammatory potential of ethanolic extract from Serjania erecta leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: The infusion of Serjania erecta Radlk (Sapindaceae) (popular name "cipó-cinco-folhas") leaves is used in popular medicine to treat back pain. The anti-inflammatory, anti-hyperalgesic and anti-nociceptive properties of the ethanolic extract from S. erecta leaves (EESE) has not been yet completely clarified. AIM OF THE STUDY: The present study investigated the anti-hyperalgesic, anti-nociceptive and anti-inflammatory properties of EESE in experimental models in mice. MATERIAL AND METHODS: EESE was fractionated by chromatographic techniques and the compound was identified by nuclear magnetic resonance (NMR), infrared (IR) spectrum, ultraviolet (UV) methods. Mice received a single dose of EESE by oral route (30, 100, and 300 mg/kg, p.o.) and were submitted to nociception induced by formalin, pleurisy induced by carrageenan and peritonitis induced by zymosan models. Mice also received EESE (30 and 100 mg/kg, p.o.) for 22 days in Complete Freund Adjuvant (CFA) model and another group received EESE for 7 days (30 and 100 mg/kg, p.o.) in pleurisy induced by Bacillus Calmette-Guerin (BCG). The cytotoxicity (MTT), phagocytic and chemotactic inhibitory activities of EESE were performed in in vitro assays. RESULTS: The fractionation of EESE led to the identification of kaempferol-3-O-α-L-rhamnopyranoside. The oral administration of all doses of EESE decreased the nociceptive response induced by formalin. EESE significantly inhibited leukocyte migration in carrageenan-induced pleurisy and zymosan peritonitis models. The daily administration of EESE during for 7 days inhibited the leukocyte migration and the mycobacteria growth of pleural material obtained from animals which received BCG. EESE significantly reduced edema, cold allodynia and mechanical hyperalgesia responses induced by CFA. EESE did not induce cytotoxicity, and also decreased the leukocyte phagocytic activity, as well as, neutrophil chemotaxis. CONCLUSIONS: EESE showed analgesic and anti-inflammatory properties in acute and persistent experimental models in mice. EESE also reduced in vitro leukocyte chemotaxis and phagocytic activity without inducing cytotoxicity. The continuous oral treatment with EESE was effective against hyperalgesia and inflammation and these results could explain the popular use of S. erecta as an analgesic natural agent.

Antinociceptive and anti-inflammatory properties of aqueous extract obtained from Serjania marginata Casar leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Serjania marginata Casar (Sapindaceae Family) Leaves are popularly used against abdominal pain. Antiulcer properties of S. marginata were scientifically described, however rare studies showed the antinociceptive effects of this plant. AIM OF STUDY: In this study, we investigated the antinociceptive and anti-inflammatory effects of aqueous extract obtained from Serjania marginata leaves (AESM) in nociception/inflammation models. MATERIAL AND METHODS: AESM was analyzed in FIA-ESI-IT-MS and Mass spectrometer LTQ XL. AESM oral administration (p.o.) (30, 100 and 300 mg/kg), dexamethasone subcutaneous injection (1 mg/kg, s.c.) and morphine (5 mg/kg, s.c.) were tested against the acetic acid-induced nociception, carrageenan-induced acute inflammatory paw edema/hyperalgesia, formalin-induced nociception and carrageenan-induced pleurisy in Swiss mice. RESULTS: Flavonoids rutin was detected in the phytochemical analysis of this extract. Oral treatment of AESM 300 mg/kg significantly reduced the number of acetic acid-induced abdominal writhing. AESM (100 and 300 mg/kg) significantly inhibited formalin-induced nociception, mechanical hyperalgesia and paw edema in carrageenan-model. Furthermore, AESM significantly inhibited leukocyte migration and protein exudation in the carrageenan-induced pleurisy test. CONCLUSION: This study confirms the antinociceptive, and anti-inflammatory activity of AESM, which may explain, in part, the popular use of this plant as a natural antinociceptive agent. This pharmacological action can be caused by flavonoids such as rutin and other compounds present in AESM.

Safety evaluation of ondansetron after gestational exposure on male reproductive parameters in rats.

Ondansetron is a 5HT3 receptor antagonist widely used to treat hyperemesis gravidarum, although its safety is still questionable. Since 5HT3 receptors, which are the target of this drug, can interfere with brain development through changes in neurotransmitter levels, this study evaluated whether the prenatal exposure to this drug could compromise reproductive and behavioral parameters in male offspring. Pregnant rats were treated with ondansetron (1.7 and 2.5 mg/kg/body weight; gavage), from gestational day 1-21. No exposure-related changes in clinical signs, body weight, food consumption, pregnancy length, and necropsy findings were observed in dams. Ondansetron exposure did not alter the anogenital distance or age of preputial separation in male offspring. Similarly, males exposed to therapeutic doses of ondansetron did not exhibit changes in play behavior. In adulthood, there were no changes in sperm parameters, as well as in testosterone level, sexual behavior and fertility. Furthermore, ondansetron did not interfere with testicular and epididymal histology, and with androgen receptor expression in hypothalamus. In conclusion, prenatal exposure to ondansetron did not cause maternal toxicity, as well as did not interfere with reproductive parameters of male offspring, indicating its safety after gestational exposure in rats.

Potential anti-arthritic and analgesic properties of essential oil and viridiflorol obtained from Allophylus edulis leaves in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Viridiflorol was identified and isolated from the essential oil of Allophylus edulis leaves (EOAE). A. edulis was used as "tereré", which is a drink made by the infusion of herbs in cold water, to treat pain (toothache and headache). All anti-nociceptive (analgesic) and anti-arthritic properties of EOAE and viridiflorol have not been completely scientifically clarified. AIM OF THE STUDY: The aim of the present study was to investigate the analgesic (anti-hyperalgesic and anti-nociceptive) and anti-arthritic properties of EOAE and viridiflorol using in vivo models. MATERIALS AND METHODS: The oral administration (p.o.) of EOAE (30, 100 and 300 mg/kg), viridiflorol (30, 100 and 200 mg/kg), morphine (1 mg/kg, subcutaneous route (s.c.)) and the intraplantar (local) administration (i.pl.) of viridiflorol (100 µg/paw) were tested using formalin model in Swiss mice. EOAE (100 mg/kg, p.o.), viridiflorol (200 mg/kg, p.o.), and dexamethasone (1 mg/kg, s.c.) were tested by zymosan-articular inflammation and in open-field models. Viridiflorol (0.3, 20 and 200 µg/paw) was also tested in carrageenan model, and viridiflorol (200 µg/paw) was also tested in tumor necrosis factor-α (TNF-α), and dopamine (DOPA) models. RESULTS: The oral administration of EOAE (100 and 300 mg/kg, p.o.), viridiflorol (200 mg/kg, p.o.), morphine (1 mg/kg, s.c.) (MOR) and local administration of viridiflorol (100 µg/paw) significantly inhibited edema and nociception in formalin model. Oral treatments with EOAE and viridiflorol (200 mg/kg) did not cause motor impairment in the open field test since they did not reduce locomotor activity. EOAE, viridiflorol and dexamethasone significantly reduced mechanical hyperalgesia, edema, total leukocytes, polymorphonuclear cells, nitric oxide and protein exudation in the zymosan-induced articular inflammation model. The local administration of viridiflorol (200 µg/paw, i.pl.) significantly inhibited mechanical hyperalgesia and edema induced by carrageenan, TNF-α and DOPA. CONCLUSIONS: This study confirms the potential anti-arthritic, anti-nocicepttive and anti-hyperalgesic properties of EOAE and viridiflorol. These properties could explain, at least in part, the folk use of A. edulis against including pain (toothache and headache). Viridiflorol could be partially responsible for the EOAE anti-hyperalgesic, anti-nociceptive and anti-arthritic properties and its mechanism of action could involve the inhibition of TNF-α and DOPA pathways.

Lactational exposure to venlafaxine provokes late repercussions on reproductive parameters in male rat offspring.

Exposure to selective serotonin reuptake inhibitors can affect hormone-dependent processes, such as the brain sexual differentiation. Because the use of these antidepressants cause concern during lactation, we evaluated the possible effects of venlafaxine on lactational exposure and its late repercussions on reproductive parameters in male rats. Lactating rats were exposed to venlafaxine (3.85, 7.7, or 15.4 mg/kg/body weight; gavage), from lactational day 1 to 20. Venlafaxine and O-desmethylvenlafaxine residues were found in all milk samples of dams treated, demonstrating the lactational transfer of this antidepressant to the offspring. Although the maternal behavior was normal, the dams presented an increase in urea and uric acid levels in the groups treated with 7.7 and 15.4, respectively, as well as a spleen weight increased in the 3.85 and 15.4 groups. The male offspring showed a decrease in play behavior parameters in the intermediate dose group. Sperm analysis indicated a reduction in sperm motility in all treated groups. The androgen receptor expression in the hypothalamus was decreased in the highest dose group, although the sexual behavior had not been affected. In conclusion, venlafaxine was transferred through breast milk and promoted changes in play behavior, sperm quality, and hypothalamic androgen receptor (AR) content, which may indicate an incomplete masculinization of the brain of male offspring.

Long-term reproductive effects of benzo(a)pyrene at environmentally relevant dose on juvenile female rats.

Since studies on the reproductive consequences after the exposure to environmentally relevant doses of Benzo(a)pyrene (BaP) during critical stages of development are scarce, this study evaluated female reproductive parameters of adult rats exposed to a low dose of BaP during the juvenile phase. Female rats (Post-natal 21) were treated with BaP (0 or 0.1 µg/kg/day; gavage) for 21 consecutive days. During the treatment, no clinical signs of toxicity were observed. Nevertheless, the ages of vaginal opening and first estrus were anticipated by the BaP-exposure. At the sexual maturity, the juvenile exposure compromised the sexual behavior, as well as the placental efficiency, follicle stimulating hormone levels, placenta histological analysis, and ovarian follicle count. A decrease in erythrocyte, platelet, and lymphocyte counts also was observed in the exposed-females. Moreover, the dose of BaP used in this study was not able to produce estrogenic activity in vivo. These data showed that juvenile BaP-exposure, at environmentally relevant dose, compromised the female reproductive system, possibly by an endocrine deregulation; however, this requires further investigation.

Nutritional evaluation of crambe meal as a partial replacement of soybean meal in Nile tilapia diet.

A variety of plant protein sources have been evaluated in aquafeeds. Crambe meal (CM) has potential for inclusion in fish diets because of its nutritional composition. This study evaluated the apparent digestibility coefficient (ADC) of crambe meal and its potential to partially replace soybean meal (SM) protein in Nile tilapia Oreochromis niloticus diets. The ADC for dry matter, crude protein, ether extract, energy, amino acids, calcium and phosphorus of CM were assessed in fish (n = 80; 65.30 ± 5.32 g). Subsequently, an 80-day feeding trial was conducted with Nile tilapia (n = 140; 6.04 ± 0.25 g) randomly distributed in 20 experimental cages (70 L; seven fish cage-1) allocated in five circular tanks (1000 L) in a recirculation water system, to evaluate the effects of replacement of SM by CM (0, 6, 12, 18 and 24% in isonitrogenous and isoenergetic diets) on growth, blood parameters, fillet yield and proximal composition. The CM shows good digestibility of protein (0.824) and amino acids (0.844) by Nile tilapia and its inclusion in the diet does not affect carcass and fillet yield or proximal composition. Fish fed diets with 24.0% of the SM replaced by CM showed the worst weight gain and feed conversion rate. The protein efficiency ratio decreased in fish fed diets with 12.0, 18.0 and 24.0% of the SM replaced by CM. Hemoglobin, mean corpuscular hemoglobin concentration, total plasma protein, glucose and alanine aminotransferase enzyme activity trend to increase at highest levels of CM in the diet. In conclusion, CM has high digestibility of protein and amino acids for Nile tilapia. However, anti-nutritional factors present in untreated CM interfere on the growth and nutrient utilization of Nile tilapia.

Preclinical safety evaluation of the ethanolic extract from the aerial parts of Gomphrena celosioides Mart. in rodents.

The toxicological potential of the ethanolic extract from Gomphrena celosioides (EEGC), a medicinal plant used as a natural analgesic, was investigated in acute and subacute toxicity models in rodents. For the acute toxicity test, 2000 mg/kg of EEGC was administered orally to male and female Wistar rats, while Swiss mice received 75, 150 or 300 mg/kg of EEGC for the subacute toxicity test. Animals treated with an only dose of 2000 mg/kg EEGC showed no clinical signs of toxicity, indicating that the LD50 is higher than this dose. The repeated treatment with EEGC did not cause adverse clinical signs, or lesions in target tissues. According to the Globally Harmonized System of classification, the EEGC dosages can be in Category 5 which is the least toxic or non-toxic one.

Can maternal exposure to tamoxifen compromise sperm and behavioural parameters of male rat offspring?

Tamoxifen, a selective non-steroidal estrogen receptor modulator, is the standard adjuvant endocrine treatment for breast cancer. Since information on the risk of using tamoxifen during pregnancy is still scarce, this study evaluated whether the in utero and lactational treatment with this drug could compromise reproductive and behavioural parameters in male offspring. Pregnant Wistar rats were exposed to three doses of tamoxifen (0.12; 0.6; 3 µg/kg), by gavage, from gestational day 15 to lactational day 20. Tamoxifen exposure did not alter the anogenital distance in the male offspring; however, there was a significant increase in the body weight in the 0.12 µg/kg dose and a decrease in the 0.6 µg/kg dose. The male offspring treated with the highest dose exhibited a delay in the onset of puberty, evidenced by an increase in the age of preputial separation. Regarding sperm parameters, there was an increase in the sperm count in the cauda epididymis in the intermediate and highest dose groups, in addition to an increase in the number of static sperm and a decrease in the progressive sperm in the same groups. Moreover, an increase in the number of hyperplasia of the epithelial clear cells was observed in the epididymis. In conclusion, the present study demonstrated that maternal exposure to tamoxifen compromised the installation of puberty of the male offspring and the maturation of the epididymis, affecting sperm storage and motility in the adult life.